Low-flow, low-gradient (LF-LG) aortic stenosis with depressed left ventricular (LV) ejection fraction is a diagnostic challenge that is frequently encountered in the management of valvular heart disease. True-severe LF-LG aortic stenosis is amenable to valve replacement, whereas pseudo-severe aortic stenosis requires management of the underlying cardiomyopathy. This distinction is important as it serves as a critical branch point in guiding therapeutic decisions. We present the case of a 71-year-old male with LF-LG aortic stenosis who had a reduced and biphasic augmentation of LV flow during dobutamine stress echocardiography (DSE). Further evaluation revealed a stenotic left subclavian artery proximal to the left internal mammary artery graft to the left anterior descending (LAD) artery. Bypass of the subclavian stenosis reversed the LAD territory ischemia and confirmed pseudo-severe aortic stenosis on repeat DSE. Traditional DSE parameters are inconclusive in patients with LF-LG aortic stenosis with poor flow reserve. Calculation of the projected orifice area or measurement of aortic valve calcium via multidetector computed tomography (MDCT) may be required in this scenario. Most importantly, reversible causes of LV dysfunction identified during DSE for LF-LG aortic stenosis require a different treatment approach than that of true aortic stenosis.

Background: Given high on-treatment mortality in heart failure (HF), identifying molecular pathways that underlie adverse cardiac remodeling may offer novel biomarkers and therapeutic avenues. Circulating extracellular RNAs (ex-RNAs) regulate important biological processes and are emerging as biomarkers of disease, but less is known about their role in the acute setting, particularly in the setting of HF. Methods: We examined the ex-RNA profiles of 296 acute coronary syndrome (ACS) survivors enrolled in the Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education Cohort. We measured 374 ex-RNAs selected a priori, based on previous findings from a large population study. We employed a two-step, mechanism-driven approach to identify ex-RNAs associated with echocardiographic phenotypes (left ventricular [LV] ejection fraction, LV mass, LV end-diastolic volume, left atrial [LA] dimension, and LA volume index) then tested relations of these ex-RNAs with prevalent HF (N=31, 10.5%). We performed further bioinformatics analysis of microRNA (miRNAs) predicted targets' genes ontology categories and molecular pathways. Results: We identified 44 ex-RNAs associated with at least one echocardiographic phenotype associated with HF. Of these 44 exRNAs, miR-29-3p, miR-584-5p, and miR-1247-5p were also associated with prevalent HF. The three microRNAs were implicated in the regulation p53 and transforming growth factor-beta signaling pathways and predicted to be involved in cardiac fibrosis and cell death; miRNA predicted targets were enriched in gene ontology categories including several involving the extracellular matrix and cellular differentiation. Conclusions: Among ACS survivors, we observed that miR-29-3p, miR-584-5p, and miR-1247-5p were associated with both echocardiographic markers of cardiac remodeling and prevalent HF. Relevance for Patients: miR-29c-3p, miR-584-5p, and miR-1247-5p were associated with echocardiographic phenotypes and prevalent HF and are potential biomarkers for adverse cardiac remodeling in HF.

BACKGROUND: In the ongoing efforts to reduce cardiac perfusion dose (injected radioactivity) for conventional SPECT/CT systems, we performed a human observer study to confirm our clinical model observer findings that iterative reconstruction employing OSEM (ordered-subset expectation-maximization) at 25% of the full dose (quarter-dose) has a similar performance for detection of hybrid cardiac perfusion defects as FBP at full dose. METHODS: One hundred and sixty-six patients, who underwent routine rest-stress Tc-99m sestamibi cardiac perfusion SPECT/CT imaging and clinically read as normally perfused, were included in the study. Ground truth was established by the normal read and the insertion of hybrid defects. In addition to the reconstruction of the 25% of full-dose data using OSEM with attenuation (AC), scatter (SC), and spatial resolution correction (RC), FBP and OSEM (with AC, SC, and RC) both at full dose (100%) were done. Both human observer and clinical model observer confidence scores were obtained to generate receiver operating characteristics (ROC) curves in a task-based image quality assessment. RESULTS: Average human observer AUC (area under the ROC curve) values of 0.725, 0.876, and 0.890 were obtained for FBP at full dose, OSEM at 25% of full dose, and OSEM at full dose, respectively. Both OSEM strategies were significantly better than FBP with P values of 0.003 and 0.01 respectively, while no significant difference was recorded between OSEM methods (P = 0.48). The clinical model observer results were 0.791, 0.822, and 0.879, respectively, for the same patient cases and processing strategies used in the human observer study. CONCLUSIONS: Cardiac perfusion SPECT/CT using OSEM reconstruction at 25% of full dose has AUCs larger than FBP and closer to those of full-dose OSEM when read by human observers, potentially replacing the higher dose studies during clinical reading.

Background: It is generally assumed that left ventricular hypertrophy (LVH) in aortic stenosis (AS) is a compensatory adaptation to chronic outflow obstruction. However the advent of TAVR has stimulated more focus on AS in older patients, most of whom have antecedent hypertension (HTN). Accordingly our aim was to investigate the interaction between HTN and AS on LV remodeling in contemporary practice. Methods: We studied 33 consecutive patients with AV peak velocity (PV) >2.5 m/s on their initial echo and a PV of >3.5 m/s on a subsequent study performed at least 5 years later. Patients’ demographics and clinical information were collected. Peak intraventricular pressure (IVP, mmHg) was defined as the sum of systolic arterial pressure and peak intraventricular gradient.Data were analyzed using descriptive statistics, paired- samples T test, and linear correlation. Results: Of our sample (46% women, mean age of 82±11 y), 29 (88%) had a history of hypertension. The average interval between the two echo studies was 6.2±1 years. As expected, wall thickness, LV Mass, and relative wall thickness increased over time. There was no correlation between change in LV mass index (LVMi, g/m2) and peak IVP, PV or AV MG. However change in LVMi did correlate inversely with baseline LVMi (r= -0.37, p= 0.03). Conclusion: Most patients seen in our practice with severe AS have antecedent hypertension and LVH. LVH worsens in parallel with worsening severity of AS. Remodeling in these patients features increasing concentric remodeling of the LV, rather than LV dilation. Given these findings, we speculate that regression of LVH to normal will not be effected by AVR because LVH proceeded hemodynamically severe AS. Strict control of blood pressure might be of equal importance in preventing and ameliorating pressure overload in these patients.

Aortic stenosis (AS) is the prototypical pressure overload lesion. The Gunther-Grossman paradigm of the 1970s dictates that as afterload increases, concentric hypertrophy—increases in left ventricular (LV) mass index and relative wall thickness—normalize systolic load and allow for normal ejection fraction despite markedly increased intraventricular systolic pressure. In some individuals, this compensatory process appears to be excessive and can be associated with poor outcome even with aortic valve replacement (AVR). Increasingly, attention has been focused on the malefic consequences for diastolic function of such ‘compensatory’ hypertrophy.